While it is generally recognized that activation of the renin-angiotensin system (RAS) is a primary initiating factor in hypertension that follows acute renal artey stenosis (RST), the precise mechanisms by which peripheral resistance is increased during this acute phase have not been determined. Further, the mechanisms which maintains renal hypertension in the established phase is unknown, although evidence for enhanced sympathetic vascular tone has been implicated. Recent evidence by the applicant indicates neurogenic tone may be increased even at the onset of RH by an action of AII on the brain and by activation of renal afferent nerves from the affected kidney. This proposal will examine the general working hypothesis that sympathetic tone is increased during the initial stage of RH and persists in the established phase when the influence of the RAS becomes diminished or absent. Arteriolar pressure, diameter, and flow in the cremaster muscle will be measured to determine microvascular resistance in the cremaster skeletal muscle of decorticate, unanesthetized rats during acute RST. Local pharmacological interventions will allow determination of alterations in neural, humoral, and myogenic components. Effects of RST on directly recorded splanchnic nerve activity and baroreflex interactions will also be obtained in decorticate rats during acute RH, and during established RH to determine if central AII sensitivity is increased at this time. Examination of renal nerve mechanisms in acute RH will be conducted in conscious, unrestrained rats, chronically instrumented for regional Doppler flowmetry. Responses to RST will be studied during RAS blockade (captopril) before and after denervation of the affected kidney. Analysis of central sensitivity to AII in established renal hypertension and possible modulation by renal afferent nerves will allow further evaluation of mechanisms responsible for the maintenance of renal hypertension. The proposed studies will use "state of the art" techniques to determine how the RAS and sympathetic nervous system interact to increase resistance. This issue is at the forefront of investigations of basic cardiovascular control and mechanisms of hypertension.